Characterization of the human argininosuccinate lyase gene and analysis of exon skipping.

A cosmid clone containing the entire human argininosuccinate lyase gene was isolated and characterized. The gene is approximately 35 kb in length and is divided into 16 exons. The sequence surrounding all splice sites was determined, and one unusual 5' splice site sequence in which a GC dinucleotide occurred instead of the consensus GT dinucleotide was observed. The exon structure of the gene is identical to that of the rat and similar to that of the delta-crystallin genes in the chicken. The transcription initiation site was identified, and 252 bases 5' of that site were sequenced. Within that region, the GC content is 75%, no TATA element was observed, and multiple potential Spl and CACCC binding sites were noted. Also, a putative consensus sequence that may play a role in the regulation of urea cycle genes was identified within this region. Analysis of the structure of the mature mRNA derived from this gene revealed that the sequences encoded by exon seven were deleted in approximately 5-10% of the mature mRNA in all tissue sources examined.